Validated Reversed-Phase HPLC-PDA Quantitation of Three Nitrosamine Impurities in Valsartan Tablets Using Selective Acidic Sample Preparation

Given the regulatory importance of nitrosamine control in sartan medicines, reliable and accessible methods are needed for their determination in finished pharmaceutical products. In this study, a reversed-phase high-performance liquid chromatography method with photodiode array detection was developed and validated for the quantitation of selected nitrosamine impurities in valsartan tablets. The target impurities were N-nitrosodimethylamine, N-nitrosodiethylamine, and N-nitrosodibutylamine. Sample preparation with dilute aqueous formic acid was used to limit valsartan solubilization and facilitate matrix removal before HPLC-PDA analysis. Chromatographic separation was achieved on a Hypersil Gold C8 column with gradient elution using ammonium formate–methanol mobile phases, and detection was performed at 228 nm. Calibration curves were linear over the concentration range of 20 to 150 ng mL−1 for N-nitrosodimethylamine and 5 to 37.5 ng mL−1 for N-nitrosodiethylamine and N-nitrosodibutylamine. Quantitation limits (QLs) were 20 ng mL−1 for NDMA and 5 ng mL−1 for both NDEA and NDBA. Accuracy ranged from 97.2 to 108.2% of nominal, and total precision ranged from 0.8 to 9.5%. The method was applied to commercially available valsartan tablets, in which none of the target nitrosamines was detected above its respective detection limit. Environmental performance, practical applicability, analytical performance, and innovation were assessed using MoGAPI, BAGI, RAPI, and VIGI, respectively. The method is suitable for routine monitoring of NDMA, NDEA, and NDBA in valsartan tablets using conventional HPLC-PDA instrumentation.